Aluminum hydroxide-metal hydroxide antacid and process of making the same



United States Patent 3 239 416 ALUMINUM HYnRoxrnE-METAL rrvnnoxmn QSRTIQCID AND PROCESS 0F MAKING THE Andrew M. Rubino, New Providence, N.J., assignor, by

mesne assignments, to Armour Pharmaceutical Company, Chicago, 111., a corporation of Delaware No Drawing. Filed May 29, 1963, Ser. No. 283,975 14 Claims. (Cl. 167-55) This invention relates to an antacid cogel and more particularly to cogels of aluminum hydroxide and one or more nontoxic alkaline earth metal hydroxides, and to a process of making the same. The antacid cogels of the invention have extraordinarily low sodium contents, below 0.005%; they can be produced at a cost as low as one third that of present antacid systems, and they have a constant and sustained buflering capacity against those acids found in gastric juices, being capable of stabilizing pH within the range of about 3 to about 5 for one hour or longer. The antacids of this invention are of great value in combatting stomach acidity, particularly where treatment with antacids of the prior art is complicated by cardiac ailments.

Antacid preparations are now quite generally employed for the treatment of peptic ulcers, gastric hyperacidity and dyspepsia. Gwilt, Livingstone and Robertson in the Journal of Pharmacy and Pharmacology, X No. 12, 770- 775 (1958), describe the characteristics of an ideal antacid. They point out that it should show its maximum neutralizing effect in the shortest possible time, that it should neutralize an adequate amount of gastric hydrochloric acid and maintain its action during the normal period of gastric digestion, that any excess however great beyond the amount required to neutralize free gastric acid should not cause alkalization, that it should raise the pH of the gastric contents to a level at which pepsin activity is reduced significantly but not totally inhibited, that adequate and repeated doses should be palatable to the hyperacid patient, and that its use should not lead to laxative, constipating or other side effects such as gastric irritation. In addition to these factors the antacid composition should be inexpensive and it should not deteriorate significantly in any respect on aging. These workers summarize the various statements in the literature as to the pH ranges desirable for the ideal antacid, and conclude that a pH within the range from about 3 to about 5 is apparently the optimum to ensure adequate relief from hyperacidity, particularly if an ulcer site is present, and at the same time permits sufiicient residual pepsin activity to avoid secondary digestive disturbances.

Modern therapeutic practice has thus abandoned the administration of excessive quantities of strong antacids such as the hydroxides of the nontoxic alkaline earth metals as they are too alkaline. Milk of magnesia (magnesium hydroxide), for example, produces a pH well beyond the optimum range of 3 to 5, reaching values as high as 9. This excessive pH, i.e., beyond the permissible upper limit of 5, is sustained for a long period. As a result, while pepsin activity is inhibited the activity of other enzymes capable of causing gastric irritation is promoted. To avoid such excessive pH rises while providing an antacid of constant and sustained activity, modern practice favors the use of acid buffers, such as aluminum hydroxide, either alone or in blends with other materials to maintain the gastric acidity at physiologically more desirable levels.

Edwards in The Chemist and Druggist, December 14, 1957, page 647, in discussing the properties of an ideal antacid has suggested that the nearest approach to the ideal attained as of that date was wet activated alumina gel. Dr. Edwards views on the properties of the ideal antacid are in substantial agreement with those expressed by Gwilt et a1.

3,239,416 Patented Mar. 8, 1966 Though liquid aluminum hydroxide gel closely approaches the ideal for an antacid, its liquid form makes it inconvenient to use, especially in the case of ambulatory patients. The liquid gel is quite rapid in its action and gives a prolonged antacid effect in the optimum pH range. It is not significantly affected in its antacid properties by pepsin, and it also does not significantly lose its antacid characteristics on aging. However, as Edwards and others have pointed out, it may have a mildly constipating effect, which many have sought to remedy by combining it with other ingredients such as magnesium hydroxide or carbonate.

The advantages of the dried gel are obvious. However, the obvious material, dried aluminum hydroxide gel, is actually far from an ideal antacid. It exhibits an undesirable lag in its rate of reaction with stomach acids. It does not give a prolonged antacid efiect in the optimum pH range, and its antacid properties are severely affected by pepsin. Also, its antacid activity is less than that of the liquid gel, being decreased by the drying and the reduced activity decreases further with aging. These disadvantages have been noted by Gwilt et al. and other workers in this field.

In order to surmount the disadvantages inherent in the use of aluminum hydroxide as an antacid, various mixtures thereof with other bases and basic salts have been tried by those skilled in the art, so as to achieve a sustained buffering action within the desired pH range. Among such mixtures has been that described by Loewig German Patent No. 70,175, who adds slowly a solution of an alkali metal aluminate to a solution containing an excess of magnesium bicarbonate, obtaining aluminum hydroxide gel and magnesium carbonate in a composition he gives as Al H O MgCO which is washed, dried and powdered. The product contains approximately equal molar proportions of aluminum and magnesium, calculated as the oxides. However, this product is rather slow reacting, not different in this respect from dried aluminum hydroxide gel.

Beekman U.S. Patent No. 2,797,978 showed that the product obtained by precipitating magnesium carbonate in the presence of aluminum hydroxy carbonate gel was superior to Loewigs in reaction velocity and in acidconsuming capacity. Beekmans product was identified as aluminum magnesium hydroxy carbonate, and is obtained by precipitation at a pH of about 8. It contains a relatively small amount of magnesium, from 5 to 25% Mg calculated as MgO for parts of the total magnesium and aluminum oxides.

The Beekman aluminum magnesium hydroxy carbonate has in fact established a high standard of antacid eilectiveness, not equaled by other proposed combinations. The composition is far superior to dry blends of aluminum hydroxide and magnesium carbonate, which cannot maintain pH within the optimum range of 3 to S for more than about one half hour.

Scheuk, Schweizerische Nedizinische Wochenschoift No. 51, pp. 1418-20 (1954) proposed at 3:1 mixture of Al(OH) and Mg(OH) which he showed was better than aluminum hydroxide gel alone. However, initially there is a high pH rise above 5, to 6 or 7, which is undesirable. The Beekman composition on the other hand, holds the pH at above 3 and never exceeding 4.5 for well over 2 hours.

Both US. Patent No. 2,880,136 and British Patent No. 745,493 coprecipitate aluminum hydroxide and one or both of magnesium and calcium carbonates at a pH of about 8.5. However, this coprecipitate also gives a rapid initial pH rise to more than 6, and the pH remains above the maximum of 5 for over an hour.

Schenk US. Patent No. 2,948,626 describes a process for making an antacid which involves reacting sodium aluminate with magnesium bicarbonate and carbon-dioxide. The product of this reaction is the aluminum magnesium hydroxy carbonate of the Beekman patent. Analysis of the product obtained by the Schenk examples confirms that the product is amorphous, has no X-ray diffraction spectra, corresponds to a mixture of the above chemicals by infrared analysis, and has the same approximate Al O MgO, Na O and CO content, pH and acidconsuming capacity of the Beekman product. It acts as though it were the same antacid in the Holbert, Noble and Grote test.

Because it has a low magnesium oxide content, the Beekman aluminum magnesium hydroxy carbonate has a low or no cathartic acivity. This is not advantageous, if cathartic activity is desired to overcome the constipat ing effect of the aluminum hydroxide gel. However, it has not heretofore been possible to prepare an antacid with a high magnesium oxide content that will not also give a rapid and too high initial pH, well above 5, because of the high alkalinity of magnesium oxide. The Schenck Al(OH) -Mg(OH) blend is an example of the effect of the magnesia. Mg(OH) -MgCO systems also have a high pH; even a 1:3 blend has a pH of 10.4.

Another characteristic to be desired of an antacid for.

some uses is that it have a low sodium content. This is an essential for treatment of gastric disturbances or.

uclers in patients having liver or heart diseases requiring low sodium or low salt diets. Antacids containing aluminum hydroxide gel are particularly prone to have I the antacids are produced. Sodium contents of 2% 012 more are frequently found. Beekman, Journal of Pharmaceu-tical Sciences, 51 No. 7, 679-682 (1960) has attempted to produce low sodium content aluminum hydroxide gels and has succeeded in reducing sodium eontents to about 0.02 to 0.03% by substitution of potassium salts for sodium salts in the manufacturing process. However, even these low levels may be too high for some patients, and antacids produced by Beekmans proposed method would be as much as 25% more expensive than comparable products of higher sodium content.

In accordance with the invention, there is provided a process for making an antacid cogel composed of a mixture of aluminum hydroxide and one or more nontoxic alkaline earth metal hydroxides.

In this process, an aluminum chlorhydroxide having from one to four atoms of chlorine per molecule is reacted with one or more nontoxic. alkaline earth metal or bismuth compounds at a pH within the range from 5 to 9, to obtain an antacid cogel which has a much lower sodium content than the antacids of the prior art, and can contain substantially higher concentrations of the alkaline earth metal or bismuth hydroxides than other similar products. Hence, the cogel is fast acting, even in the form' of a dried gel. It demonstrates a prolonged antacid activity within the optimum pH range .of from about 3 to about 5, and does not display an undesirable high initial pH rise. Because of the low sodium content, it can be administered without fear of inducing edema or ascites in patients having heart or liver diseases.

The aluminum hydroxide-nontoxic alkaline earth metal I or bismuth hydroxide cogel antacids produced in accordance with the invention closely approach the requirements for an ideal antacid. In either wet or dry form they. are capable of quicky increasing the pH of gastric juices to within the range of from about 3 to about 5. They maintain the pH within this optimum range for prolonged periods of time, in excess of one hour. They do not display the initial high pH rise characteristic of systems containing alkaline earth metal or bismuth hydroxides, yet they can contain concentrations of the alkaline earth metal hydroxides sufficient to overcome the constipating effects associated with aluminum hydroxide. They are non-systemic, and do not upset the acid-base balance of the blood; They are not adversely affected in antacid action by pepsin, and they are not irritating to the gastrointestinal tract. Furthermore, they can be prepared at costs astlow as one third those of presentjantacid sys-- terns, because of the process of their preparation.

Although the antacid of the invention can bedescribed chemically as an aluminum-nontoxic alkalineearthlmetal or bismuth hydroxide, this is not meant ,toimply that it is a single chemicalcompound, since the composition and structure are as yet'unknown. The aluminum, ;non-:

toxic alkaline earth .metal, or bismuth, and hydroxyl groups may be associated in some form of co-mplexio n or coordination complex, or the product of this invention maybe a simple mixture. But, even though free alkaline earth metal or bismuth hydroxide is present, the antacid characteristic of the. cogel antacid product differ substan.-. tially from conventional blends of aluminum hydroxide and alkaline. earth metal or bismuth hydroxide: having a comparable alkaline earth metal or bismuth hydroxide content. The cogel antacids of the invention do not display the undesirably high'initial pH riseheretofore experienced with materials of comparable alkaline earth metal or bismuth hydroxide content.

The proportions of aluminumhydroxide and alkaline earth metal or bismuth hydroxide in the cogel antacids are quite critical indeveloping and maintaining a fast antacid action within the pH range of from about 3 to 1 about 5. The molecular ratio of the hydroxides is.ex-. pressed herein for simplicity as the. weight 4 ratio MO:Al O3where M is one or more of the alkaline earth metals or bismuth. This ratio is not critical,and usually is within the range of from 1:20 to 10:1, and preferably from 1:2 to 5:4.

The ,antacid cogels of the invention are conveniently prepared by adjusting the pH. of a water solution of an aluminum .chlorhydroxide and one :or more nontoxic alkaline earth metal and/or :bismuth compounds to a pH within the range from about 5 up to about 9,; and preferably up to about 8, at which the .desired cogel product precipitates as a gel or slurry. The presence of the nontoxic alkaline earth metal and/ or bismuth CORP,

pound is required to obtain-an effective antacid, as increasing the pH of the aluminum chlorhydroxide in the absence of the alkaline earth metal and/or bismuth compound will produce an .Al(OH) gel of unsatisfactory antacid properties.

The composition of the cogel formed when the pH is increased is a function of the concentration of the alkaline earth metal and/ or bismuth in the mixture, and the final pH of the cogel slurry. The higher pHsE and higher alkaline earth metal or bismuth concentrations favor higher MO:Al O weight ratios, whilethe flower pHs= and lower alkaline earth metal or bismuth concentrations favor lower MO:Al O :weight ratios. V

The aluminum chlorhydroxidesrused in this invention. are water-soluble mild acids containing from one to-four.

atoms of chlorine per molecule. Their pH 20% water solution=varies from about 2.5 rfor the basic Al (OI-I) Cl to about 4.4 for the /6' basic Al (OH)' Cl.. A preferred material is the highly concentrated (50 wt'.

droxide, magnesium sulfate, calcium sulfate, calciumcarbonate, magnesium carbonate, calcium chloride, magnesium chloride, calcium nitrate, magnesium nitrate, bis- ;muth subcarbonate and bismuth hydroxide.

The pH of the mixture maybe increased by addition ;of,any of the alkali metal or bismuth carbonates such as sodium and potassiumcarbonates either in solidform or in aqueous solution; the word carbonate is used genermetal hydroxides and ammonium hydroxide are notsatisfactory as, if used, a cogel of unsatisfactory antacid characteristics is formed.

:Theantacidsof the invention are formed by combining the aluminum chlorhydroxide .with the alkaline earth .metal orbismuth compound in aqueous solution or suspension. These reactants can be added to the reaction mixturein anyorder or together. .The .pH-increasing carbonate or hydroxide can. beadded to the. reaction mixture at any time, before or after the reactants are combined, but as required to maintain pH within the range from 5 to .9 during the reaction.

Temperature control ofthesolution below a predetermined maximum during the processing procedure is important since, should the temperaturerise above theperof the solution would be difficult to avoid. The maximum temperature depends uponthe choice of method used to jadjustthe pH. Room temperatures usually are preferred. Where the alkali metal carbonate-s are used, a temperature of j50 C. has been foundto be themaximum and a temperature below 40 C. is preferred. Where a nontoxic alkalineearth metal or bismuth hydroxide is used,

: a temperatureof 60 C. is the maximum, and a temperature below 50 C. is preferred.

The antacid cogels of the invention are formed as a water gel or slurry when the pH of the mixture is increased. The slurry formed in this manner may be chilled to assist in completing precipitation of the cogel. The

slurry canalsobe aged for a period of time, usually for :30 minutes to several hours, again to ensure complete precipitation, and also to allow time to complete com- ,Pl in 9 th ccmpon 1 con th r-an vci of e invention.

ft th r ac ar compl t d. t e og can be separated from the solution by means known to those skilled in the art suchas, for example, vacuum filtration or centrifugation. Since the nature of the separated cogel is such as to minimize the amount of occluded or adsorbed salts, the recovered cogel may readily be freed of soluble salts, and especially of soluble sodium salts, by washing with deionized water. Thus, use of alkali metal compounds in adjusting pH does not lead to a high alkali metal content in the product, unlike aluminum hydroxide itself, whose occlusion tendencies are notorious.

The amount of wash water required to achieve a sodiumfree antacid cogel may vary widely and can, most advantageously, be determined empirically, i.e., by repeated washings until analyses of the cogel show that the desired sodium content in the product has been achieved. In general, washing the product with a volume of deionized Water equivalent to three times the initial slurry volume has proved satisfactory.

' The antacid cogel can be marketed as a wet gel or slurry or, alternatively, as a dry product. The antacid product in either the wet or dry form may contain small amounts of carbonate ion or carbon dioxide, usually within the range of from about 0.2% to about in wet gel suspensions, as a function of the secondary cation being employed and/ or the process. For example, preparation of calcium carbonate and magnesium basic carbonate in situ results in high carbon dioxide contents, and also is .a function of MO:Al O ratio. This carbonate or carbon dioxide represents material occluded in the cogel in the process of manufacture, or material adsorbed by the cogel in storage, and is not significant to either the process or the performance of the cogel antacid product. Basic carbonate species may be present:

plus other cations such as Mg Ca++, etc., which can also react with carbonates prior to or after bonding to aluminum, etc. In some cases, calcium carbonate or magnesium basic carbonate can be for-med in situ, or calcium carbonate can be added as such, so that carbonates must be presumed to be present in these cases.

The dry form of the cogel product may be obtained by any convenient method known to those skilled in the art, such as, for example, spray drying, tray drying or vacuum filtration. The dried cogel will usually contain less than 25% free water and, if necessary, can be reduced to powdered form for convenience in marketing. In the powdered form the antacid cogel is a finely divided, white, tasteless, and odorless solid which reacts readily with gastric acid containing pepsin. For greater convenience the cogel antacid products of the invention can also be prepared in tablet form, and, since the product is relativelyinert and stores well, the tablets can be prepared by conventional procedures. The product can be tabletted as such, or with the aid of the customary exci-pients, such as, for example, a polyol, a sweetener and a lubricant such as mannitol, dextrose and magnesium stearate. The following is a typical tablet formulation:

Gram-s Antacid composition 32,000 Lactose a- 62,620 Starch 6,800 Monosodium phosphate 1,130 Stearic acid 1,130

The quantity indicated is sufficient to prepare approximately 48,000 tablets containing 10 grains each of the antacid composition.

Those skilled in the art will perceive other methods for the administration of the composition and it will be apparent that these are in no way critical but can be selected to meet any particular requirements.

The following examples, in the opinion of the inventor, represent the best embodiments of the invention.

The antacid characteristics were determined by two methods.

The first method used is that of Holbert, Noble and .Grote, Journal of the American Pharmaceutical Association (Scientific edition), 36 149 (1947); 37 292 (1948); 41 361 (1952), as modified by Stewart M. Beekman, 49 191 (1960). In this method, a test sample of antacid is added to 150 ml. of artificial gastric juice consisting of 0.0316 N hydrochloric acid (pH=1.5) containing 2 g. of pepsin NF. per liter. The acidity can be varied, but this normality is adopted solely as a test standard for evaluation of one antacid vis-a-vis another. The artificial gastric juice is maintained at a temperature of 37.5 C. The test procedure is carried out by continuously introducing fresh artificial gastric juice, beginning with the tenth minute of the test period, and removing the antacidgastric juice mixture by overflow at the rate of 2 ml. per minute. The .antacid effect is determined by measuring the pH of the artificial gastric juice during .the test period, which is two hours or longer.

The method of Bachrach as reported by Hinkel, Fisher and Tainter, J. Am. Pharm. Ass., 48 380 (1959) was also used. This method consists essentially of adding dilute hydrochloric acid to the antacid at 37.5 C. at such a rate as to maintain a predetermined pH, usually 3.5 or 3.9.

This method gives a direct estimate of the speed of action and total available acidity, whereas the Holbert,

Noble, and Grote test procedure demonstrates primarily the butferingeiiect, as measured by pH and duration of action. In the test procedure as used in this work, the

acid used was 0.0875 N hydrochloric acid, containing 2. The acidity canbe:

grams of sodium chloride per liter. varied, but this normality is adopted solely as a test standard for evaluation of oneantacid vis-avis anothen.

EXAMPLE 1 87.0 grams of a 50% (weight basis) water solution of the /5 basic aluminum chlorhydroxide [Al (OH)' Cl] were added toan agitated vessel containing 126 gms. of a magnesium hydroxide slurry (21% MgO) and 1825 rnls; H O over a minute period. During this period agitation was continued andthe solution was maintained at a temperature of 50 C. by the use of a hot plate. Following the addition, the mixture was aged fora period of one hour during which agitation was continued and the temperature of the mixture was maintained at 50 C. At the end of this period the pH of the mixture was 6.9. Thereafter, the pH of the mixture was adjusted to 8.5 with 113 g. of 10% (wt. basis) Na CO solution added over a 5 minute period. The resulting slurry was filtered to recover the cogel antacid and the filter cake was washed six times with deionized water, each wash being equivalent in volume to about half that of the original slurry. 250 g. of the washed filter cake was then reslurried in 35 cc. of deionized water and homogenized to produce a thick, creamy, white antacid cogel suspension containing about 2.05% A1 0 and 2.02% MgO.

. Table I A1 0 equivalent, wt. percent 2.05 MgO'equiValent, wt. percent 2.02 Al O :MgO ratio, wt. basis 1:1 pH (2% A1 03 resuspension) 8.7 Na+ ion nil Cl ion -percent 0.001 CO content Acid consuming capacity 1 16.4 Cc. N/10 HCl per gm. of suspension 2 16.0 Viscosity, centi-poises 204 The antacid characteristics of this suspension as determined by the modified Holbert, Noble and Grote test procedure is shown in Table IV.

Table II pH of artificial gastric juice Tune (mmutes) (10 cc. dose of antacid suspension) EXAMPLE 2 i 1 218 grams of a 20% (wt. basis) aqueous isolutio'n of Al (OH) Cl wasadded over .a one=11ourperiod to a: mixture of 86 gms. of a magnesiurmhydroxide slurry; (21% MgO(OH) 10.6 g. N'a CO and 1730 mls.-H O'.

The temperature during addition was maintained at 28 C. The pH after the addition was completed was, 8.35.

The resulting cogel antacid was aged for :two hours at 25.30 C. and then filtered, washed and reslu rried as in' Example 1.

Table III; 7

A1 0 equivalent, wt. percent 2.16; Mg() equivalent, wt. percent 2.695 Al O :MgO ratio, wt. basis pH (2% A1 0 resuspension), L 8.8 Net ion nil (11- ion percent 0. 26

CO content a; Acid consuming capacity, cc. N/ 10 HCl per "gm.

of suspension 1 24.8 Viscosity, centipoises '604 The antacid characteristics ofthis suspensionas determined by the modified Holbert, Noble and G-rote test procedure are shown in:Table. IV.

Table IV pH of artificial gastric juice Time (mmutes): ('10 cc. dose ofantacid suspension) 0 1.65 A 2.2. /2 2.35, 1 2.5 2 3.2.. 3 4.15 4 4.3 5 4.4 6 4.45. 7 4.50 s 4.60 9 4.65 10 4.70 20 .4.45 30 ..4.40 4O 4.30 50 4.25" 4.20 4.15 4.10 4.05: 3.90 3.50 3.0 f 2.5. 4 2.4 g

The data of Example 2 shows that the antacid com- 7 position was capable of maintaininga pH within the range of from 3 to 5 for a periodof to 120 minutes.

The time initially required to reach a pH-above 3 was 3 I -m1nutes. The antacid did not increase the initial: pH?" to above 4.7 even=at high concentrations of the alkaline earth metal hydroxide.

EXAMPLE 3 p A .basic aluminum chlorhydroxide Al (OH)' Cl solution :was prepared from Chlo'rhydrol and aluminum chloride, and aged in dilute aqueous solution for two 1 10% aqueous solution ofsodium carbonate over a period.

grams of a white gel was isolated.

19 of one half'hour. The slurry was then aged for four hours, filtered and washed in a Buchner funnel. 418.8 This gel was made into an aqueous suspension (2.25% aluminum oxide) byone hours agitation in water with a Lightnin mixer,

plus hand homogenizing.

The gel analyzed as follows:

MgO 2.10%. Mg0/Al O w./w. ratio 0.92: 1.00.

Fe 34 p.p.rn. A.C.C. at pH 3.5 17.5.

A.C.C. at pH 3.9 17.0.

Arsenic Less than 1 p.p.rn. Heavy metals Less than ppm. Viscosity 348 cps.

This antacid gel was tested by the Holbert, Noble and Grote modified test procedure, using a cc. dose with the following results:

Time (minutes): pH 1.85 0.25 2.4 0.5 2.5 1 2.8 2 3.7 3 4.2 4 4.3 5 4.35 6 4.4 7 4.45 8 4.5 9 4.5 10 4.55 4.5 4.35 4.2 4.0 3.8 3.75 3.7 3.6 3.45 3.3 3.1 3.0 2.9 2.8 2.7 2.6 2.5

The data show that the antacid gave a pH of over 3 in slightly over one minute, and maintained the pH at above 3 for 120 minutes. The highest pH reached was 4.55.

EXAMPLES 4 TO 6 Three antacid suspensions were prepared, having differing MgO:Al 'O ratios, according to the following procedure.

(4) 126 grams of 60D magnesium hydroxide gel (21% MgO), 106 grams of sodium carbonate and 1690 ml. of water were slurried together (the final pH was 11.1), and to this slurry was added 218 grams of a 20% by weight aqueous Chlorhydrol solution, dropwise, over a period of 55 minutes. At the end of this period, the pH was 8.2. Carbon dioxide was then bubbled in at 20 psi. for 20 minutes, after which the pH was 7.45, and the slurry was then aged for 2 hours to a final pH of 7.65.

The slurry was filtered, and the filter cake washed six times with 1000 ml. of deionized water. Filtration, washing and compression took about 4 hours. The filtrate was clear with a pH of 8.5. A white compressed antacid gel was collected, and an aqueous suspension made from it by agitating with water in a Lightnin mixer for one hour and then hand homogenizing.

(5) This procedure was repeated, employing 86 grams of the 60D magnesium hydroxide (31% MgO), 218 grams of the 20% Chlorhydrol solution and 1640 ml. of water. The Chlorhydrol solution was added dropwise over one hour, and then a stoichiometric amount (101 grams) of a 10% aqueous sodium carbonate solution was added all at once.

(6) The procedure was repeated a third time, using a stoichiometric amount of sodium carbonate and magnesium hydroxide, slurrying them together as in the first case using 276 grams of the 60D magnesium hydroxide (31% MgO), 31.8 grams of sodium carbonate and 5190 ml. of water. 652 grams of the 20% aqueous solution of Chlorhydrol was added to this slurry over a period of one hour, after which the final pH was 8.5. The slurry was allowed to age for 'four hours, filtered, and the filter cake washed with 750 ml. of deionized water.

The assay data for each of these antacid suspensions was as follows:

Example 6 A120 percent 2. MgO, percent 1 M ro/A1 03, w./ v pH A.C.C. at pH 3 A.C.C. at pH 3.9.

ratio Na 00 percent. 0.98 0.38

Viscosity, eps 1, 386 Fe, ppm

EXAMPLES 7 TO 9 Three dry antacid powders were prepared in accordance with the following procedure:

(7) 65 grams of 60D magnesium hydroxide (21% MgO) was slurried in 911 ml. of Water, and heated to 60 C. 44 grams of a 50% aqueous solution of Chlorhydrol Al (OH) Cl was added all at once, and the whole was reacted for one hour at 60 C. The slurry was then cooled to room temperature, after which the pH was 7.1, and filtered in a basket-type centrifuge, washing the solid material with 3000 ml. of deionized water. 233 grams of a White antacid gel was recovered, which was dried in an air oven at 45 C., and ground through a 0.2 inch mesh herringbone screen on a Mikro sample mill, yielding 24.8 grams of a soft white powder.

(8) 120.5 grams of compressed antacid gel obtained in accordance with Example 4 was dried in an air oven at 45 C. for eight hours, and ground through a 0.2 inch mesh herringbone screen on a Mikro sample mill, yielding 23.4 grams of a soft white powder.

(9) 319 grams of a /3 basic aqueous aluminum chloride Al (OH) Cl solution containing 6.45% A1 0 was added to a slurry of 86 grams of 60D magnesium hydroxide (31% MgO) in one hour in 1450 ml. of deionized water. Next, 200 grams of a 10% aqueous sodium carbonate solution was added all at once. The slurry was aged for four hours to a final pH of 8.55, filtered and washed with deionized water. 350.9 grams of a white antacid gel was isolated. 217.8 grams of this gel was dried for eight hours at 45 C. in an air dryer, and ground through a 0.2 inch mesh herringbone screen on a Mikro sample mill to yield 24 grams of a soft white powder.

Example 7 Example 8 Example 9 A1203, percent 30. 3 26. 5 27. 5 MgO, percent 26.9 32. 9 32. 2 MgO/Al Oa, w./w. ratio 0.89:1. 1. 24:1. 00 1. 17: 1. 00 Cl, percen 3.18 0.03 0.05 a Na, percent 0.005 Nil 0.02 Fe, p.p.m 430 470 715 Reaction velocity (Muteh) 245 116 135 Reaction velocity (Reheis) 50 26 1 A.C.C. at pH 3.5 213 239 277 A.O.C. at pH 3.9 197 234 271.

The powders of Examples 8 and 9 were subjected to the Holbert, Noble and Grote modified test procedure, using a 1 gram dose, with the following results:

P P Time Time- Minutes Minutes Example 8 Example 9 Example 8 Example 9 The data show that both these antacids were capable of maintaining the pH at above 3 for 125 to 135 minutes. The pH in the case of Example 8 exceeded 5 only momentarily and very'slightly, and in the case of Example 9,

was below 5 throughout this period.

EXAMPLES 10 TO 12 Three antacid suspensions were prepared, according to the following procedure:

(10) 218 grains of aqueous Chlorhydrol solutionwas added over a one hour period to 86 grams of a dilute slurry of magnesium hydroxide 60D (31% MgO) slurried in 1540 ml. of water. The final pH was 6.4. Then, 167 grams of a 10% sodium bicarbonate solution was added to the slurry over a hour period to a final pH of 8.3. This slurry was aged for four hours to a pH of 8.6, filtered through a Buchner funnel and washed with deionized water. 397.7 grams of a white compressed antacid gel was recovered. An aqueous gel suspension was made by agitating with water in a Lightnin mixer for one hour, and hand homogenizing.

(11) A dilute solution (319 grams) of /a basic aluminum chloride Al (OH) Cl (6.45% A1 0 was added a over a one hour period to 86 grams of a dilute slurry of magnesium hydroxide 60D (31% MgO) in 450 ml. of deionized water to a final pH of 5.05. 394 grams of a 10% aqueous sodium bicarbonate solution was introduced to this slurry over a /2 hour period, to a final pH of 8.20. This slurry was aged for four hours to a pH of 8.55, filtered and washed with deionized water. 289.3 grams of a white compressed antacid gel was recovered. An aqueous gel suspension was made from this gel by agitating with water in a Lightnin mixer for one hour,

and hand homogenizing.

(12). 218 grams of a 20% aqueous Chlorhydrol so-. lution was added to 86 grams of a slurry of magnesium hydroxide 60D (31% MgO) and 17 grams of sodium bicarbonate in 1730 ml. of water, over a one hour period to a pH of 8.45. The slurry was aged for four hours,

filtered and washed with. deionized water; 304 4 grams of a white antacid gel was isolated, and made? into an aqueous suspension by agitating for one hour. with water in a Lightnin mixer, and hand homogenizing.

These antacid gel suspensions analyzed as. follows:

Example 10 Example 11 Example 12 A1 0 percent 2. O3 1. 69 2. 28 MgO, percent 2. 48 1. 86 2. MEG/A1203, w./w. ratio--- 1.22:1. 00 1 10:1. 00 1.22:1. pH 8. 75 8.4 8. Na, percent. 0.002 0. 001- 0.00 01, peroent 0. 015 Nil" N11 002, Percent" 0.33 0.19 0.55 Fe, p.p.m 35 45 40 Heavy metals, p.p.m- 5 5 5 Arsenic, p.p.m 1 1 1 11.0.0. at pH 3.5"- 18. 05 15. 2 19. 97 11.0.0. at pH 3.9 17; 8 15. 0 19. 8

EXAMPLE 13 86.7 gram of a 50% aqueous; Chlorhydrol solutionand 134 grams of MgCl -6HgOiflakes, were dissolved in This solution wasthen added in one hour to a solution of Na CO 58% Na O in 1000 mls. The end pH was 8.6. After aging for four hours, the pH was 8.55, at which time the precipitate was filtered through No. 1 What'man paper -oi1- Buchner funnels, and washed with deionized water. 376.2

1300 mls. of deionized water;

grams of a white compressed antacid gelcake was isolated, and an aqueous suspensionwas made therefrom,

which assayed as follows:

86.7 grams of'the 50% Chlorhydrol solution and .134 grams of MgCl 6H O,flakes, were dissolved in 1000 mls.

of deionized water. 83.6 grams of N-a CO 58% Na O,

was dissolved in 1000 mls.-of deionized water. Both solutions were heated to C. and then they were added simultaneously to a four liter beaker. The :precipitate was reacted at 70 C. for '20- minutes. Next, it was quenched with 1500 mls. of dcionizedwater.

with deionized water. 457.9 gramsyof a white compressed antacid gel cakewas isolated :andan aqueous suspension was made therefrom, which assayed as fol lows:

MgO 1.4%.

'MgO/Al O w./w. ratio 0.71/1.00.

Cl .nil.

Fe .37 p.p.m.

A.C.C. at pH 3.5 i 14.8 cc.N/1'0CHl/gm.

suspension.

A.C'.C. at pH 3.9 14.5 cc. N/lOHCl/g suspension.

Viscosity -1. 1880 cps.

The prec1p1tatc was filtered through Buchner funnels and Washedv 13 EXAMPLE 15 63.6 grams of the 50% Chlorhydrol solution was diluted with 96 mls. of deionized water and added, in one hour, to a slurry of 49.4 grams Mg(OH) 60D slurry, 29% MgO, 47 grams CaCO U.S.P., heavy powder, precipitated, and 7.8 grams -Na CO 58% Na O, in 1956 mls--of deionized water. The end pH was 7.85. The precipitate was aged for one hour, filtered through No. 1 Whatm-an paper on Buchner funnels, and washed with deionized water. 278.9 grams of a white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

A1 1.55%. MgO 1.6%. CaO 2.58%. MgO/CaO/Al O w./w. ratio 1.03/1.66/1.0. pH 8.75. Na 0.004%. Cl 0.004%. CO 2.96%. Fe 33 p.p.m. Heavy metals 3 p.p.m. Arsenic 1 p.p.m. A.C.C. at pH 3.5 22.7 mls./g. A.C.C. at pH 3.9 22.4 mls./g. Viscosity 290 cps.

EXAMPLE 16 47.2 grams of the 50% Chlorhydrol solution and 130 grams of CaCl -2H O, were dissolved in 1000 mls. of deionized water. This solution was then added, in one hour, to a slurry of 21.5 grams Mg(OH) 60D slurry, 29% MgO, and 79.3 grams Na CO 58% Na O in 1000 mls. deionized water. The end pH was 7.0. After aging for one hour, the pH rose to 7.2, at which time the precipitate was filtered through No. 1 Whatman paper on Buchner funnels and washed with deionized water. 263.6 grams of a white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

A1 0 1.08%. MgO 0.66%. CaO 3.83%. MgO/CaO/Al O w./w. ratio 0.61/3.54/1.00. P 9-0 Na 0.04%. C1 0.004%. CO 2.34%. Fe p.p.m. Heavy metals 3 p.p.m. Arsenic 1 p.p.m. A.C.C. at pH 3.5 20.3 mls./g. A.C.C. at pH 3.9 20.1 mls./ g. Viscosity 121 cps.

EXAMPLE 17 72.3 grams of the 50% Chlorhydrol solution was diluted with 109 mls. of deionized water and added, in one hour, to a'slurry of 89 grams Mg(OH) 60D slurry, 29% MgO, 20 grams CaCO U.S.P. powder, heavy, precipitated, and 8.9 -gramsNa CO 58% Na O in 1860 mls. of deionized water. The end pH was 8.0. After aging for one hour, the pH was 8.6, at which time, the precipitate was filtered through No. 1 Whatman paper on Buchner funnels and washed with .deionizer water.

291.5 grams of a white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

5 MgO 1.88%.

CaO 0.62%. MgO/CaO/Al O w./w. ratio 1.81/0.6/1.00. pH 8.8.

Cl nil.

Fe 23 p p In Heavy metals 1 p.p.m. Arsenic 3 p.p.m.

A.C.C. atpH 3.5 15.7 mls./g. A.C.C. at pH 3.9 15.4 mls./g. Viscosity 78.7 cps.

This gel suspension was subjected to the. Holbert,

Noble and Grote modified test procedure, using a 10 cc.

dose, with the following results:

Time (minutes): pH 0 1.95 0.25 2.7 0 5 2.85 1 3.05 2 4.0 3 4.45 4 4.65 5 4.8 6 5.0 7 5.2 8 5.4 9 5.6 10 5.8 20 7.1 30 6.8 6.35 5.15 40 4.35 4.25 3.95 3.45 3.05 45 103 3.0 2.9 2.85

50 EXAMPLE 18 86.7 grams of the 50% Chlo-rhydrol solution was diluted with 131 mls. of deionized water and'added, in one hour, to a slurry of CaCO U.S.P., heavy powder, precipitated, and 10.7 grams Na CO 58% Na O in 1850 5 mls. of deionized water. The end pH was 7.35. After aging for one hour, the pH rose to 7.5, at which time the precipitate was filtered through No. 1 Whatman paper on Buchner funnels and washed with deionized water. 320.6 grams of a white compressed antacid gel cake was 60 isolated and an aqueous suspension was made therefrom,

which assayed as follows:

A1 0 2.37%. CaO' 2.95%.

65 CaO/Al O w./W. ratio 1.24/l.00.

Na 0.002% Cl 0.011% CO 3.74%

70 Fe 18 p p 111 Heavy metals 10 p.p.m. Arsenic 1 p.p.m. A.C.C. at pH 3.9 19.2 mls./g. Viscosity 19.0 mls./g.

75 A.C.C. at pH 3.5 814 cps.

15 EXAMPLE 19 80:7 g a sef the 50% Cirlerhydrol solution'was diliitd with 131 nils. of deionized water and added, in one hour, to as urryor 5 grams CaCG U.S.P., heavy powder,

idlsfi df de idnized water: rtreea pn was 7.15.: After aging for one hour, th pH rose to 7.5, at which time the precipitate was filtered through N6. 1 Whatrnan paper on a Buchner funnel and washed with deioniz'e'd water.- 253.4 grams *ofa white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as tollowsr QaO/AI O fade 0.085/1.0%.

Heady metals piplmz Arsenic 1 ppm ACC.atpH V A.C.C. at pH 3.9 -..a

Viscosity EXAMPLE 20 86.7 grams of the Chlorhydrol solution and 272 grams of CaCI -ZH O were dissolved in 1500 mls. of deionized water. This solution was added, in one hour, to a solution of 164.7 grams of Na CO' 58% Na O in 2000 mls. of deionized water. 'The end pH was 6.7. After aging for one hour, the pH was still 6.7, at which time a the precipitate was filtered through No. 1 Whatman paper on Bu'ehner funnels andwashed with deionized water. 462.7 grams of a white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

A1 0 1.07%. gao hsfi 4.1%. Qa/Al ratio 3.83/10 ;;-==-=:LE= 8J2; Na 0.014%. or 000.2%. 002

13:13.11! Heavy rnetals 10 5. 5.111.-

firfi-ffi: at 3.5 s 18.5 mls./g. A.C.C. at pH 3.9 .s 18.3 mls./g, Viscosity -5;. 120 cps.

EXAMPLE'Zi 86.7 grams at the 50% Chldrhydfol seiatian was at luted with 131 mls. of deionized water and added, in one hour, to a slurry of 8.2 grams Mg(OH) ,'60D slurry,

29% MgO, and 10.7 grams of Na CO 58% Na o in 700 f mls. of deionized water. After aging one hour, the pH was 8.5, at which time the precipitate was filtered through No. 1 Whatman paper on a Buchner funnel and Washed with deionized water. 258.1 grams of a white compressed antacid gel cake was isolated and an aqueous suspension wasmade therefrom, which assayed as follows:

A1 0 2.06% MgO 0.31%. MgO/Al O w./w. ratio OAS/1.00. pH 8.2.

Na 0,0003%. 7 C1 0.004%; CO 0.5%.

Fe 10 ppm. Heavy metals 10 ppm. Arsenic 1 ppm. -A.C.C. at pH 3.5- 11.8.

A.C.C. at pH 3.9 11.5;

Viscosity 229 cps.

165:; EXAMPLE 22.

86.7 grams ofthe 50% Chlorhydrol solution was diluted with 131' mls. of deionized water and added, in one hour, to. aslurry of 269 grams Mg( OI-I)' 60D slurry,

5 39% MgO, and 10.7 grams Na CO 58% Na o in soon mls. of deionized water. The end pH was 8.05. aging one hour, the pH rose to 8.7, at which time the precipitate was filtered through No. 1 Whatman paper:

on Buchner funnels aud washedlwith deionized water. 448.3 grams of a whiteqcompressedantacid gel cakewas isolated and an aqueous suspension was made therefrom, which assayed as follows: i

was prepared by reacting 86.7 grams of the 50% Chlorhydrol solution and 24.2 grams concentrated HCI, Reagent Grade, then diluted with. 131 imlsl:ofdeionized water. This solution was thenadded, in one hour, to a slurry of86'grams Mg(;OH) 60D slurry. 39% MgO, and 24 grams.Na CO'3,- 58% Na O,,in 1500mls. of deionized water. The and pH. was, 7.7. After aging for I one hour, the. pH rose to 8.05,'at which time the pre- 40 cipitate .was filtered throughsNo. 1 Whatman paper on Buchner funnels and washed with deionized water. 298.7

grams of a white compressed antacid gel 'cake wasdsolated and. an aqueous suspension was made. therefrom, which assayed as follows:-

. Arsenic. 1 p.p.m

A.C.C.atpH-3.5 ,26.1." V A.C.C.at pH 3.9 a 25.9. Viscosity 872 cps.

. EXAMPLE 24 5.2 grams of bisrnuthltrinitratefiH o crystals, 48% Bi O was dissolved in" a solution of ;118.3 grams of concentrated nitric acid, Reagent Gradelin 1000 mls; of deionized Water.: To this solution 1110 grams of 50% NaOH solution was, added dropwise over a one hour period... The ;resulti was a thin slurry .of a -white precipitate at pH 11.4. 10.7 grams of Na CO 58% 'Na O, was dissolved in this slurry and a solution of 105.3 grams.,50%-Ch1o'rhydrol solution and 132 mls. of. deionized water was added in 60 minutes. The pHwas 8.75. After aging one =hQur,-the pH was 8.8, at which time the precipitate was filtered through No. 1 What-, man'paper. :on a Buchner funnel and washed with d6.

ionized water. 265.6. grams of a white compressed After 17 antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

A1 4.0%. Bi O 0.38%. Bi O to A1 0 w./w. ratio 0.095 to 1.00. pH 8.1. A.C.C. at pH 3.9 15. cc./ gm. suspension. Viscosity 300 cps.

EXAMPLE 25 10.4 grams of bismuth trinitrate-H O crystals, 48% Bi O was dissolved in a solution of 238 grams of concentrated nitric acid, Reagent Grade, in 2000 mls. of deionized water. To this solution, 149 grams of Na CO 58% Na O, dissolved in 400 mls. of deionized water, was added in 60 minutes. The pH was 6.45.

An excess of 10.7 grams Na CO 58% Na O, was dissolved in this slurry and the pH recorded at 9.25. Next, a solution of 85 grams of the 50% Chlorhydrol solution in 132 mls. of deionized water was added in one hour. The pH was 7.2. After aging one hour, the pH was 7.5, at which time the precipitate was filtered through No. 1 Whatman paper on a Buchner funnel and washed with deionized water. 231.5 grams of a white compressed antacid gel cake was isolated and an aqueous suspension was made therefrom, which assayed as follows:

Bi O 1.0%.

Bi O to A1 0 w./w. ratio 0.25 to 1.00.

A.C.C. at pH 3.9 14.7 cc./ gm. suspension. Viscosity 13 cps.

Equivalent antacid dosages yield equivalent neutralizaing results, irrespective of whether a wet form of the antacid slurry or a resuspension of its dried powder form is used. The antacids can thus be administered with equal effectiveness in wet or dry forms.

For comparison with the antacids of the invention, three aluminum hydroxide-magnesium hydroxide slurries were prepared as follows:

(A) 110.5 g. of a thick reactive suspension of aluminum hydroxide compressed gel was mixed with 72 g. of magnesium hydroxide wet paste and slurried in 418 g. of deionized water.

(B) 108.2 g. of a thin suspension of a reactive aluminum hydroxide compressed gel was mixed with 72 g. of magnesium hydroxide wet paste and slurried in 420 g. of deionized water.

(C) 80.8 g. of a highly concentrated aluminum hydroxide gel having a somewhat lower reactivity than the above aluminum hydroxide compressed gel was mixed with 72 g. of magnesium hydroxide wet paste and slurried in 447 g. of deionized water.

The mixture were agitated at 1000 r.p.m. in a Lightnin mixer for one hour, and were then homogenized through a hand model homogenizer.

Analysis of the above three suspensions indicated an A1 0 content of 1.86%, an MgO content of 2.5% and an Al O :MgO weight ratio of 121.3 in each instance. The pH of the slurry of Sample A was 8.15, of Sample B 8.5, and of Sample C 8. The acid consuming capacity of these was 23.5, 24.3 and 22.8 cc. N/ HCl per g. of suspension, respectively. The antacid effectiveness of the above three suspensions was determined by the Holbert, Noble and Grote procedure for a 10 cc. dose and is tabulated in Table V together with the comparable Example 2.

1 3 Table V Example (minutes) N o. 2

A B C A comparison of the acid neutralizing characteristics of the above prepared mixed gels of the prior art with Example 2 indicates that the mixed gels A, B, and C tend to over-neutralize, i.e., have initial pH rises above the maximum permissible level of 5.

A portion of each of the slurries of Samples A, B, and C was air dried at 45 C. in an air circulating oven for 32, 27.5 and 23.5 hours, respectively, and pulverized to yield a soft white powder.

The antacid effectiveness of the three powders was determined by the Holbert, Noble and Grote test procedure using a one gram dose. The results are presented in Table VI together with the comparable Example 3.

Table VI Example (minutes) No. 3

A B O The above data indicates that the dried powder made from the mixed gels also tended to over-neutralize. The pH remains above 5 for /2 hour and the pH is maintained within the desired range only for the last two hours of the minute test period.

The antacid cogels of this invention are thus shown to be different from and more effective than mere mixtures of the gels of the individual components. It is unusual and unexpected to obtain a coprecipitated gel or slurry which is more reactive than a simple mixture of its comsequent over-neutralization.

ponents. The alkaline earth metal hydroxides are normally characterized by a high initial pH surge with con- This undesirable characteristic of these hydroxides is masked in the antacids of this invention while their desirable cathartic properties are retained, to counteract the constipating eifect of alumie acids are of great utility in the treatment of gastricidisturbances in patients where the usual treatment is made impractical or at least more complex by concomitant heart or liver diseases.

I claim:

1. A process for preparing an antacid capable, as determined by the Holbert, Noble and Grote modified test method, of maintaining the pH of artificial gastric juice within the range from about 3 to about for at least one hour, which comprises mixing in water aluminum chlorhydroxide containing from one to four chlorine atoms per molecule and a compound selected from the group consisting of nontoxic oxides, hydroxides, sulfates, chlo- I rides, nitrates, subcarbonates, carbonates and bicarbonates of the alkaline earth metals and bismuth in proportions to provide a gel mixture of aluminum hydroxide gel and a hydroxide gel selected from the group consisting of alkaline earth metal hydroxides and bismuth hydroxide in a molecular weightratio calculated as MO:Al O Within the range from about 1:20 to about :1,where M is selected from the group consisting of alkaline earth metals and bismuth adjusting the pH to within the range from about 5 to about 9 at which a cogel precipitates.

2. A process in accordance with claim 1 which comprises separating the gel mixture from the reaction mix ture and washing the gel mixture to remove soluble salts therefrom.

3. A process in accordance with claim 1 which includes drying the gel mixture.

4. A- processin accorda'nceiwith claim 1 :which corn-. prises adjusting the pH towithin' the range -from' about:

5 to about '9 by adding analkalimetal carbonate-while maintaining the temperature-below about C.

5. A processinaccordance withiclaim lpyhich COIII'. prises adjusting the pH to within the-; range from about- 5 to about 9 by adding an alkalimetal hydroxide while maintaining the temperaturebelqw about C- 7 6. An antacid prepared according to claim 1 having a pH of about 5 to about 9, a sodium, content of less than 0.005% and capable as determined by the Holbert, Noble and Grote modified test-method of maintaining the pH of artificial gastric juice Withinthe range. from about )3 to about 5 for. atleast one.'hour, comprisingan aluminum;

hydroxide gel and a hydroxide gel selected from the class consisting of. the non-toxicalkaline' earth metals and bis.- muth, in a molecular weight ratio calculated as ,MO:Al O

within the range from about 1:20 to about 10:11 wherein M represents a cation selected from the. group consisting of nontoxic alkalineiearth metals and bismuth.

. 7. An antacid in accordance with claim 6 in the form.

of an aqueous suspension.

8. zAnantacid in accordance with claim 6 in thefform of a wet gel.

9. An antacid in accordance with claim 6 in the form of a dry powder.

10. An antacid tablet comprising a composition -in' accordance with claim .6 and an excipient.

11. An antacid in accordance with claim 6 wherein the"; alkalineearth metal'is magnesium.

1Z.IAI1 antacid in accordance with claim .6 wherein the alkaline earth metal is calcium.

13. "An antacidin accordance with claim 6 wherein the alkaline earth metal is a mixture of magnesium and calcium.

14. An antacid in accordance with ,claim .6 wherein M is bismuth.

References Cited by the Examiner;

UNITED STATES PATENTS 2,570,532 10/1951 Eisenberg; 167 5 5 2,880,136 3/1959 Gore 16755 JULIAN S. LEVITT, Primary Examiner.

FRANK CACCIAPAGLIA 'JR.', Examiner. 

1. A PROCESS FOR PREPARING AN ANTACID CAPABLE, AS DETERMINED BY THE HOLBERT, NOBLE AND GROTE MODIFIED TEST METHOD, OF MAINTAINING THE PH OF ARTIFICIAL GASTRIC JUICE WITHIN THE RANGE FROM ABOUT 3 TO ABUT 5 FOR AT LEAST ONE HOUR, WHICH COMPRISES MIXING IN WATER ALUMINUM CHLOROHYDROXIDE CONTAINING FROM ONE TO FOUR CHLORINE ATOMS PER MOLECULE AND A COMPOUND SELECTED FROM THE GROUP CONSISTING OF NONTOXIC OXIDES, HYDROXIDES, SULFATES, CHLORIDES, NITRATES, SUBCARBONATES, CARBONATES AND BICARBONATES OF THE ALKALINE EARTH METALS AND BISMUTH IN PROPORTIONS TO PROVIDE A GEL MIXTURE OF ALUMINUM HYDROXIDE GEL AND A HYDROXIDE GEL SELECTED FROM THE GROUP CONSISTING OF ALKALINE EARTH METAL HYDROXIDES AND BISMUTH HYDROXIDE IN A MOLECULAR WEIGHT RATIO CALCULATED AS O:AL2O3 WITHIN THE RANGE FROM ABOUT 1:20 TO ABOUT 10:1, WHERE M IS SELECTED FROM THE GROUP CONSISTING OF ALKALINE EARTH METALS AND BISMUTH ADJUSTING THE PH TO WITHINTHE RANGE FROM ABOUT 5 TO ABOUT 9 AT WHICH A COGEL PRECIPITATES. 